Experimental delayed radiation necrosis of the brain

1979 ◽  
Vol 51 (5) ◽  
pp. 587-596 ◽  
Author(s):  
Albert N. Martins ◽  
Ralph E. Severance ◽  
James M. Henry ◽  
Thomas F. Doyle
Keyword(s):  
Rhesus Monkeys ◽  
Radiation Necrosis ◽  
Clinical Signs ◽  
Control Group ◽  
Content Type ◽  
Brain Irradiation ◽  
Primate Brain ◽  
High Doses ◽  
The Brain ◽  
Male Rhesus

✓ The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1½ days before and 10½ days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of dexamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

Craniocerebral missile injuries in the monkey: an experimental physiological model

1972 ◽  
Vol 36 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Arthur M. Gerber ◽  
Robert A. Moody
Keyword(s):  
Rhesus Monkeys ◽  
Common Factor ◽  
Blood Gases ◽  
Physiological Model ◽  
Content Type ◽  
Epidural Compression ◽  
The Brain ◽  
Strong Suspicion ◽  
Fine Print ◽  
Carotid Flow

✓ Experiments were carried out on rhesus monkeys to determine what physiological parameters were most closely correlated with death due to craniocerebral missile injuries. Observations of intracranial pressure, blood pressure, carotid flow, blood gases, respiratory rate, depth and volume, and electroencephalograms were made. These parameters were compared in survivors and nonsurvivors as were the pathological injuries. The most important single parameter that correlated with death was the drop in carotid flow. As this same correlation has been observed in epidural compression experiments in the monkey, there is a strong suspicion that reduced blood flow to the brain as measured by carotid flow is a common factor in craniocerebral missile injuries and epidural compression injuries.

scholarly journals The induced dose of experimental autoimmune encephalomyelitis was not determinant and proportional to histopathological findings

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Maiara Carolina Perussolo ◽  
Bassam Felipe Mogharbel ◽  
Lucia de Noronha ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Histopathological Findings ◽  
The Brain ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. It presents a diversity of neurologic signs and symptoms as well the incapacities. Since the need for advances in MS treatment, many studies are for new therapeutic technologies, mainly through using preclinical models as experimental autoimmune encephalomyelitis (EAE). This study aimed to observe and analyze the development in Lewis rats-induced model of EAE. Methods It was used 23 females of Rattus norvegicus, from 6 to 8 weeks, weighing around 170 g. Of 23 rats, 19 underwent EAE induction distributed in six groups to establish the evolution of clinical signs. B. pertussis toxin (PTX) doses were 200, 250, 300, 350–400 ng, and four animals as the control group. The animals had weight and scores analyzed daily, starting seven and ending 24 days after induction. Then, all animals were euthanized, and the brain and spinal cord were collected for histopathological analyses. Results The results showed that the dose of 250 ng of PTX induced de higher score and weight reduction. All groups who received the PTX demonstrated histopathological findings. Those characterized as leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brain. In the spinal cord, the loosening of the myelinated fibers was observed by increasing the axonal space in all tested doses of PTX. Conclusions EAE was not dose-dependent. Histopathological findings do not proportionally related to clinical signs, as in human patients with MS.

scholarly journals Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery

2005 ◽  
Vol 103 (5) ◽  
pp. 882-890 ◽  
Author(s):  
Noboru Kusaka ◽  
Kenji Sugiu ◽  
Koji Tokunaga ◽  
Atsushi Katsumata ◽  
Ayumi Nishida ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vascular Endothelial ◽  
Content Type ◽  
Endothelial Growth Factor ◽  
The Brain ◽  
Brain Angiogenesis ◽  
Fine Print

Object. Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks. Methods. A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group. Conclusions. In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.

The modern employee: exercise and the brain

2018 ◽  
Vol 17 (2) ◽  
pp. 62-65
Author(s):  
Pamela Guggina
Keyword(s):  
Physical Activity ◽  
Meta Analysis ◽  
Well Being ◽  
The Body ◽  
Control Group ◽  
Regular Exercise ◽  
Depression And Anxiety ◽  
Content Type ◽  
Clinically Depressed ◽  
The Brain

Purpose An area of workplace well-being, and thus performance, which is now being recognized more widely is the mental health of employees. Research today demonstrates that exercise is good for the body and dramatically affects the brain. While it is widely accepted that regular exercise can promote weight loss, lower blood pressure and decrease the risks of diabetes, heart disease and certain cancers, it is also becoming clear that exercise can improve mood, coping skills and even treat clinical depression and anxiety. These findings further support the upward trend of companies offering a wider range of health benefits to their employees. Design/methodology/approach One example of the combined research, Rethorst et al., published a large meta-analysis exploring the interaction between physical activity and depression. They examined 58 randomized trails and found that participants in the studies who had been randomized to use exercise as a treatment for depression had significantly lower depression scores than participants who had been randomized to the non-exercise or “control” group. Both clinically depressed and non-clinically depressed individuals reported lower depression scores if they participated in the exercise group. Findings Exercise can be as effective as medication in treating depression. Regular exercise can decrease the symptoms of clinical anxiety. Employers who incentivize physical activity can dramatically lower healthcare costs. Benefits packages which promote physical activity can increase productivity and decrease absenteeism. Originality/value There will always be people with an illness which requires medication, but there appears to be a group that will benefit greatly from getting out and moving with regular exercise. The hope is that physicians with patients who have symptoms of depression and anxiety will encourage their patients to get some exercise to see if it helps. This can be something that is done alone or as an adjunct to talk therapy and/or pharmacologic treatment. Exercise is not likely to change the circumstances that make life challenging, but it can help all humans cope better with these challenges.

scholarly journals Significant Reduction of Brain Cysts Caused by Toxoplasma gondii after Treatment with Spiramycin Coadministered with Metronidazole in a Mouse Model of Chronic Toxoplasmosis

2012 ◽  
Vol 56 (4) ◽  
pp. 1762-1768 ◽  
Author(s):  
Wai Kit Chew ◽  
Ignacio Segarra ◽  
Stephen Ambu ◽  
Joon Wah Mak
Keyword(s):  
Toxoplasma Gondii ◽  
Vero Cells ◽  
Toxoplasmic Encephalitis ◽  
Combination Group ◽  
Control Group ◽  
Time Curve ◽  
Content Type ◽  
Brain Cysts ◽  
The Brain

ABSTRACTToxoplasma gondiiis a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and thein vitroreactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n= 9), which received vehicle only; (ii) a spiramycin-only group (n= 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n= 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n= 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n= 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC0–∞) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC0–∞values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P< 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reducedin vitroreactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction ofT. gondiibrain cysts, with potential clinical translatability for chronic toxoplasmosis treatment.

Hypothalamic dysfunction following whole-brain irradiation

1986 ◽  
Vol 65 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Jeffrey I. Mechanick ◽  
Fred H. Hochberg ◽  
Alan LaRocque
Keyword(s):  
Computerized Tomography ◽  
Radiation Necrosis ◽  
Cortical Atrophy ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Content Type ◽  
Hypothalamic Dysfunction ◽  
Brain Irradiation ◽  
X Irradiation ◽  
Fine Print

✓ The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage.

scholarly journals MRI-based morphometric analysis in relation to Chiari-like malformation in brachycephalic canine breeds

2017 ◽  
Vol 86 (6) ◽  
pp. 351-360 ◽  
Author(s):  
C. R. Gordon ◽  
K. Marioni ◽  
P. Amengual ◽  
T. Liuti
Keyword(s):  
Morphometric Analysis ◽  
Clinical Signs ◽  
Magnetic Resonance Images ◽  
Human Condition ◽  
Control Group ◽  
Type I ◽  
Clinical Grade ◽  
Skull Morphology ◽  
Chiari Malformation Type I ◽  
The Brain

The aim of this study was to investigate potential differences and correlations between brain and skull morphology and the clinical signs of brachycephalic dogs with and without Chiari-like malformation (CLM). Various measurements were derived from magnetic resonance images of the brain and craniocervical junction of thirty brachycephalic dogs in a flexed-neck position. Each dog was assigned a clinical grade. The distance from the planum of the foramen magnum to the pons was significantly reduced, providing evidence of craniocephalic disproportion similar to human patients with Chiari malformation type I. Cerebral length relative to cranial length was significantly increased in dogs with CLM compared with control dogs, supporting the hypothesis that CLM is governed by a global overcrowding of the brain, dissimilar to the human condition. Significant correlations were identified between these measurements and the extent of cerebellar herniation. No significant differences or correlations were identified with clinical grade. This is the first described morphometric analysis to use a strictly brachycephalic study population inclusive of a control group free from CLM.

Implantation of dispersed cells into primate brain

1989 ◽  
Vol 70 (3) ◽  
pp. 441-445 ◽  
Author(s):  
Robert J. Plunkett ◽  
Stephen C. Saris ◽  
Krzysztof S. Bankiewicz ◽  
Barbara Ikejiri ◽  
Richard J. Weber
Keyword(s):  
White Matter ◽  
Human Lymphocytes ◽  
Interleukin 2 ◽  
Lymphokine Activated Killer Cells ◽  
Content Type ◽  
Primate Brain ◽  
Needle Track ◽  
The Brain ◽  
Fine Print ◽  
Dispersed Cells

✓ Although several experimental therapies such as dopaminergic cell implantation in parkinsonian models and intratumoral placement of lymphokine-activated killer cells require intracerebral deposition of dispersed cell suspensions, a successful technique of needle implantation of cells into primate brain has not been demonstrated. The authors have sought to establish a stereotaxic technique to predictably deposit dispersed cells in primate brain. Human lymphocytes were cultured in recombinant interleukin-2, labeled with sodium 51 chromate (51Cr), and stereotaxically injected into the frontal white matter of six anesthetized rhesus monkeys. A 10-µl aliquot of cell suspension (2 × 107 cells/ml) was deposited 16 mm deep to the dura at 5 µl/min via Hamilton No. 22s or 26s needles. Five control aliquots were counted for each injection. Reflux out of the needle track was absorbed on gauze, and the recovered cells were counted. The animals were sacrificed 1 hour after implantation and the brain was removed and sectioned such that the cortex and white matter along the needle track were separate. The tissue sections were then counted. Recovery was expressed as the percentage of total injected radioactivity (cpm) that was present in each brain section. Two additional injected hemispheres were processed for autoradiography and histological study. Cell recovery in the brain (mean ± standard deviation) was 87.2% ± 13.9% (3.3% ± 4.9% in cortex and 83.9% ± 15.9% in white matter). The autoradiograms and histological examination showed a dense accumulation of radioactivity (cells) at the target site and minimal radioactivity (cells) in the needle track. Accurate intracerebral deposition of dispersed cells in primates was achieved with the technique described. This knowledge permits reliable stereotaxic implantation of cells into the brains of nonhuman primates and humans for investigation and therapy.

scholarly journals Induced Neurocysticercosis in Rhesus Monkeys (Macaca mulatta) Produces Clinical Signs and Lesions Similar to Natural Disease in Man

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
N. Chowdhury ◽  
A. Saleque ◽  
N. K. Sood ◽  
L. D. Singla
Keyword(s):  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Epileptic Seizures ◽  
Cognitive Responses ◽  
Chronic Inflammatory Response ◽  
Experimental Animal Models ◽  
Liquefactive Necrosis ◽  
The Brain

Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

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